Table of contents

ad. 1. Prenatal, genetic, 3D, 4D, 4D HDlive examinations. Which of these should I undergo during pregnancy?

A lot of patients are confused when they browse examinations offers of the ultrasound centres, health centres and hospitals. New terms, like prenatal, genetic, 3D, 4D, 4D HDlive might be unclear, and as a result, cause difficulty in choosing an appropriate centre and necessary examinations.

To begin with, let us emphasize that these terms are often just pure marketing in order to draw more patients to a given centre. Pretty pictures, placed on websites, have a similar aim. Unfortunately, it is not always backed by the experience in detecting anomalies. Experience does not depend on the terms or the medical equipment, but it depends on the skills, predisposition, and knowledge of a specialist in the field of detecting congenital defects and genetic syndromes in fetuses. In fact, there are very few experienced specialists in Poland, which shows a lot of ultrasound examinations on the market in a bad light.

A questionable ultrasound image will be sent to a specialist having diagnostic experience either way, in order to properly diagnose or exclude a problem. An average OB/GYN physician, who does not have everyday contact with anomalies in ultrasound, encounters only several anomalies throughout his career, which makes it difficult for him to know what to look for and how to classify a given anomaly. A scan performed by a proper specialist reduces the entire process, always connected with the necessity to dedicate additional time to visit a specialist with an experience in this field.

The term “prenatal” appeared along with the Prenatal Program, created by the National Health Fund, ensuring ultrasound examinations in the first and second trimester for selected patients. In reality, the term “prenatal” means all the examinations performed prior to birth.The term “genetic” originated in the USA, although it is rarely used with the same meaning, as it requires analysts with experience in detecting the Down syndrome in the second trimester. A vast majority of specialists have no contact with such cases, and for this reason, this term, in our personal opinion, is highly overused in the offers (a detailed description can be found in the answer to the question: “What is genetic ultrasound examination?”). 3D and 4D, as well as 4D HDlive, are often understood by patients as more accurate examinations, but they are useful only when an anomaly has been confirmed, to specify a diagnosis, but not to exclude a congenital defect in a correctly developing fetus. 3D technique had spread commonly because of the interesting effects of a reconstructed image, which we use only as an addition during the examination, provided that a baby is properly positioned and a patient is rather slim. We do not charge for such so-called commercial 3D/4D scans because we take the position that it would be unfair giving no diagnostic benefits to a patient. In the respect of that, we do not offer 3D/4D examinations. The 3D reconstruction technique is constantly developing. There are new methods, such as HDlive mode which we tested in 2011 and 2012, but they are still only additions, having nothing in common with the diagnostic purposes of ultrasound. The requirement of proper circumstances for an examination remains unchanged, which means that we can “play” with the reconstruction only in limited cases. Of course, an image on websites or brochures will always draw attention as it is simply interesting.

The term “4D HDlive” has nothing in common with HD television. It is a kind of reconstruction of the surface of a fetal body giving interesting effects, resulting from the possibility to control virtual lighting. It has no use in the field of diagnostics. It gives good artistic impressions in an early pregnancy. Similar to other 3D reconstruction techniques, 4D requires proper examination conditions, which makes it available only for some patients and is only an addition to an examination. This kind of additions to an ultrasound examination in the form of images of faces, limbs or gender should not cover the real purpose which is an examination of anatomy and activity of a fetus. That is why, each self-respecting sonologist would not draw your attention to the images but to the assessment of the health of a baby.

To sum up, irrespective of the terms, three well-performed examinations should be conducted during pregnancy: first one, at about 12 weeks; second one between 18 and 20 weeks and the third one between 28 and 32 weeks, carried out by a specialist who knows what to look for that is the one who deals with fetal anomalies. We recommend checking the qualifications of the specialists as well as their experience in the field of detecting defects. It may save your time and the number of ultrasound scans. The medical equipment has a secondary meaning, as a detailed examination can be performed on nearly all devices currently available on the market. Please remember that even the best apparatus will not help a less experienced specialist in making a diagnosis.

ad. 2. What is a midpregnancy anomaly scan?

This is an examination carried out in the middle of a pregnancy, precisely between completed 18 and 23 weeks (that means from 18 weeks forward, not 17 weeks forward). Its aim is an assessment of the fetal anatomy along with the exclusion of the most common congenital defects. Bearing in mind the fact that ab. 33% of all the defects are heart defects, in the midpregnancy scan protocol followed by our specialists, we have included fetal echocardiography, according to the ISUOG guidelines. Our patients do not have to additionally undergo such examinations. During the exam we assess the amount of the amniotic fluid, the localization and the structure of the placenta.

ad. 3. What is a genetic scan?

The term “genetic” ultrasound is often overused, since people tend to use this word referring to every “more precise” ultrasound examination during pregnancy. However, it is defined as an element of the second trimester anomaly scan which, on the basis of a series of ultrasound markers, qualifies a given case for the amniocentesis or not. It is performed between completed 16 weeks and 20 weeks of gestation by a specialist experienced in detecting the Down syndrome (trisomy 21). Nowadays, there are a few protocols of genetic ultrasound. At our centre, we apply two of them: combined Nyberg 2001 and Bromley 2002 as well as DeVore 2000. These protocols are updated with constantly released reports. The efficiency of such an examination ranges between 75% and 91%, depending on applied protocol.

The technique of the “genetic” risk assessment (so called genetic scan) was developed in the United States earlier than the European technique of screening tests in the first trimester. It is constantly developed thanks to the experience of sonologists all over the world and it consists in detecting features of fetal appearance, which might indicate the Down syndrome. There are only a few highly qualified centres in the USA, which have genetic scan in their offer. This kind of examination is not performed in Europe nearly at all because of the “tradition” of 11 – 13+6 screening tests.

Genetic scan is recommended to:

the patients who, in the first trimester of pregnancy (11+0-13+6 weeks) did not undergo a screening test for the Down syndrome and other genetic syndromes

the patients, who after a screening test in the first trimester of pregnancy were in a group of an increased risk and refused to undergo offered diagnostic tests, e.g. amniocentesis or chorionic villus sampling.

Why is experience so important in genetic ultrasound?Detecting the Down syndrome in the second trimester might be very difficult. Not all children with trisomy 21 show anatomical defects, not all of them suffer from problems with the ossification of nasal bone or increased nuchal fold thickness. A lot of fetuses with the Down syndrome look almost identical as fetuses without anomalies. For this reason, it is highly recommended that the examination shall be performed by a specialist, who individually detected at least 20 cases of trisomy 21 in the second trimester (which is very difficult because the average occurrence of the Down syndrome is 1/1000 cases) and applies genetic ultrasound algorithms on a daily basis. Nevertheless, such a specialist should keep in mind that this method is not 100% effective and it will not detect all cases of the Down syndrome.

During an ultrasound scan chromosomes are not visible, but with a proper technique defects and certain features of a baby that are the signs of possible genetic disorders can be recognized. However, in each case it is essential to conduct a conclusive test such as amniocentesis, chorionic villus sampling or fetal blood sampling.

Neither the examination at 12 weeks not the one in the third trimester at 30 weeks can be called a genetic scan!

ad. 4. Why is it so important to undergo an anatomical examination before 20 weeks of gestation?

the ratio of the ultrasound beam width to the size of the fetus is better up to 20 weeks, this allows to apply a wider range of the transducer clearance angles and thereby to reduce the time of an examination.

up to 20 weeks the assessment of the markers for genetic disorders is most sensitive in the second trimester; in that case, beside the assessment of the anatomy of organs it is possible to perform their assessment reliably;

in questionable cases this gives time to carry out amniocentesis to identify full karyotype before 22 weeks. It allows to plan the further course of the pregnancy.

ad. 5. How to best schedule 11-13+6 weeks scan at our centre?

The Fetal Medicine Foundation guidelines clearly state the time when this examination should take place: 11 – 13+6 weeks of gestation when the crown rump length (CRL) is 45 – 84 mm. However, patients who would like to undergo this examination at our centre are strongly encouraged to register after 12 weeks, i.e. 12+, not later than 13+3 weeks (which corresponds to 60-70 mm of fetal length).

Points justifying this approach are listed below:

the test sensitivity for the Down syndrome, basing on our experience, is the highest when a patient completes 12 weeks of pregnancy and it decreases when a fetus reaches the length of 80 mm.

an appointment at 12+ guarantees that the majority of patients will fit in time with the examination and will get a result with a calculated risk for the Down syndrome and others.If we refer a patient, and we give the scope of 11-13+6 weeks, we can encounter a situation, when the real gestational age, calculated on the basis of CRL is different from the one indicated by the last menstruation. The fetus might be younger, which means that there will be a need to postpone the appointment, or older and it will be impossible to perform a precise scan with the calculation of most frequent trisomies risk.

The length between 60-70 mm optimizes the time of the scan because during this time the position of a fetus toward the long axis of the uterus is the most favorable for the examiner.

An early anatomy scan, including fetal heart assessment is possible in most cases after 12 weeks of pregnancy.

Therefore, for a couple of years, to the question “When should the first trimester ultrasound examination be conducted?” we have been answering after 12 weeks of pregnancy, i.e. 12+ a few days! Not at 11+, nor 13+.

If a patient underwent an ultrasound examination at ab. 7 weeks, the CRL was measured precisely and the gestational age was calculated reliably, the 12 weeks examination may be scheduled more exactly. For instance, CRL is 6.7 mm (6 weeks+ 4 days), which means that the best time to perform the first trimester screening ultrasound will be in 6 weeks time.

The screening ultrasound test of the first trimester at 11 – 13+6 weeks of gestation is mainly focused on the exclusion of major anomalies of fetal anatomy. The anomalies are often unrelated with genetic syndromes, e.g. acrania, extensive defects in the area of: spine, brain, limbs, diaphragm, front side of a chest and abdominal cavity, majority of the forms of the single ventricle heart defect, more severe anomalies of the bladder. The ultrasound parameters assessment for the calculation of the risk of the Down syndrome and other syndromes is an independent, additional element of the examination.NIPT (Neobona/HARMONY/NIFTY) non-invasive screening tests of high sensitivity allow to assess:

the risk of trisomies, i.e. the Down, Edwards’ and Patau syndromes

the risk of some microdeletion syndromes, e.g. DiGeorge syndrome

the risk of other chromosomal aberrations

fetal gender

The sensitivity of the NIPT method for the Down syndrome is higher than the sensitivity of an ultrasound scan, however, it is not 100%. As far as we are concerned, one false positive NIFTY result has been registered in Poland so far. The baby was born with the Down syndrome.We would like to emphasize that the latest discussions concerning NIPT examinations might create an erroneous impression that non-invasive screening tests of high sensitivity may replace an ultrasound examination of the first trimester. Considering all fetal anomalies, the Down syndrome constitutes ab. 10-15% of them, whereas fetal anatomy defects as many as 66%. The belief that NIPT tests are sufficient might delay the diagnosis of more frequent fetal anomalies.

ad. 7. Questionable results of fβ-HCG + PAPP-A test.

Every result of a biochemical fβ-HCG + PAPP – A test should be consulted with a specialist and only they can interpret the results correctly! The values of the laboratory results received by a patient are provided in international units (IU/l) or others with a quantitative characteristic. Therefore, presenting the results in certain units, essential for interpretation (a multiple of the median MoM), requires tools and medical knowledge.

Suspicious values of biochemical parameters for the Down syndrome are as follows: if the value of fβ-HCG exceeds 2.52 MoM and the value of PAPP-A is below 0.5 MoM; for Edwards’ and Patau syndrome (Trisomy 18 and 13): if the values of both parameters are below 0.33 MoM; for Turner syndrome: if value of PAPP-A is below 0.5 MoM and fβ-HCG is 1 MoM; for triploidy syndrome: if values of fβ-HCG and PAPP-A are both below 0.1 MoM or exceed 5 MoM.

Reliable biochemical examinations can be performed in laboratories carrying out a great number of tests (local population norms are important) on an accredited analyzer, e.g. Kryptor made by Brahms (available in Poland in “Diagnostyka” network), where a strict assessment of the quality of assays is maintained.

A biochemical examination should always be confronted with a detailed ultrasound scan. For example, it is possible that the biochemical results show low levels of both previously mentioned parameters, which indicates a higher risk of trisomy 13 and 18, but if an ultrasound scan (including the assessment of early fetal anatomy) does not present any anomalies, in fact, the genetic risk is not increased.

We would like to ask our patients and their partners not to interpret the results on their own, as it might lead to unnecessary stress.

ad. 8. When should I undergo a biochemical test in the first trimester (PAPP-A and fβ-HCG test)?

When the specialist in charge recommends a biochemical examination along with an ultrasound scan in the first trimester, the best time for the examination, in respect of its sensitivity, would be around 10 weeks of gestation (this is optimal timing for the key parameter- PAPP-A) . At 12 weeks the results are already available and they might be included into the genetic risk assessment at the same time as the ultrasound scan is performed. Such an approach reduces the number of appointments to the necessary minimum and it allows to interpret the patient’s blood test results together with the ultrasound scan.We often encounter the screening model, in which first a patient undergoes an ultrasound examination and on the same day she has her blood sample taken for biochemical examination, and, as a consequence, she returns home without any initial results. Next, after a week the patient receives the examination report from the medical staff, without a specialist consultation and without the possibility to discuss the results. Thus, the patient frequently seeks help in interpretation of the results on her own. Undergoing a biochemical test at 10 weeks of gestation, and an ultrasound examination when the biochemical test results are already available would allow patients to avoid the situation described above and reduce stress during pregnancy at the same time.If you have any recommendations, or you would like to include biochemical parameters into an aneuploidy risk assessment, please mention that information while scheduling the appointment. The reception desk will direct you to a laboratory accredited by the Fetal Medicine Foundation.

ad. 9. What is nuchal translucency? Increased NT

Nuchal translucency i.e. a fluid accumulated beneath the skin on the fetal neck is a typical characteristic of a baby at the stage of 11+0-13+6 weeks of pregnancy. Increased volume of the fluid (increased nuchal translucency, increased NT) is a symptom, not a disorder. Such a situation occurs in about 9% of all the examinations performed. In this case, the examiner is obliged to clarify the potential reasons of this situation, i.e. first to exclude the genetic syndromes (10% of fetuses with increased NT) and then possible congenital defects.

Very often an increased nuchal translucency is not connected with any anomaly. It is just an indication to exclude most common reasons: aneuploidies with the use of chorionic villus sampling and amniocentesis, and anatomical defects through an early fetal anatomy assessment together with the heart assessment. If the results turn out to be normal, the whole problem can be considered non-important.

The measurement of NT is reliable only if performed in the right time, i.e. 11+0-13+6 weeks of pregnancy and carried out by a specialist with a certificate of the Fetal Medicine Foundation (FMF). The list of the specialists can be found on the following website: wwww.fetalmedicine.com. Please take note that since 2008 the FMF has not required taking a practical exam, and the requirements have been lowered significantly in order to bring this method into general use. At present, a specialist can obtain the certificate after sending only three images showing NT measurement and taking part in an online course on the Foundation’s website.

In our opinion, the measurement of nuchal translucency is one of the most difficult measurements performed during the whole pregnancy, requiring a comprehensive training and good reproducibility. The difficulty consists in seizing a fetus in a particular position, proper adjusting of the machine and, in many cases, patience of a specialist and a patient. The measurement of NT has no strict norms or so-called absolute values, nevertheless, it influences the final result of an examination, i.e. the value of the computer calculated risk of chromosomal aberrations. The result in the form of a description with the calculations, but without an image showing the method of carrying out the NT measurement is incomplete (a clear documentation of the measurement is essential). In our opinion, in this area, the specialist’s experience in the first trimester examinations and detecting genetic syndromes is of the greatest importance, e. g. the Down syndrome occurs on average in 1 in 1000 pregnancies. In order to detect only 20 such cases, statistically speaking, the number of 20,000 screening tests would have to be performed, or the specialist would have to examine patients with already suspected anomalies by another specialist and analyze the further outcome of these pregnancies.

ad. 10. Nuchal translucency (NT) screening test.

In the situation when the examination of the first trimester revealed an increased NT, a lot of patients wish to undergo a check-up examination towards the issue some time later at another centre. Since they look for someone who would ease their mind, they do not pay attention to the precision of the scan, which might influence the accurate diagnosis in a negative way.

What factors should one take into consideration when seeking a second opinion? First of all, it is important to check whether the examiner holds the FMF certificate in measurement (the names of the specialists authorized can be found on www.fetalmedicine.org, in the section concerning certificates in NT: “Holders of the FMF certificate in measurement of NT”) and whether he/she is experienced (www.fetalmedicine.org, in the section concerning certificates in NT: “NT specialists with successful audit”). A very important issue is if the measurement has been done according to the regulations, which can be seen in the image of NT attached to the results. The results without the images are treated as if there was no measurement, since the image serves as a proof that the examination was performed precisely and reliably. Please note that an increased nuchal translucency is a symptom, which disappears, in both healthy and unhealthy fetuses. Therefore, the best solution would be to consult the issue immediately and if the risk of chromosomal aberrations is increased (calculated on the basis of the highest, precisely measured NT value), to undergo a test of a higher sensitivity or a conclusive examination. An isolated, increased NT in a lot of cases is not connected with any fetal anomaly, however, it might be clarified only with the use of adequate methods.

At our centre, we can perform a second opinion examination, and a conclusive test if necessary. Please mention the problem during the registration, we will schedule the appointment at the earliest convenience.

ad. 11. What does the absence of a nasal bone in the first trimester mean?

“The absence of a nasal bone” is not a very accurate term describing a state, in which the fetus has a delayed ossification of the nasal bone. A lot of patients even believe that the nose of their baby had not developed. Nothing of the kind! The nose exists in such cases. We would rather encourage to use the terms: delayed or correct ossification of the nasal bones.

In clinical understanding the term “delayed ossification of the nasal bones” between 11 and 14 weeks occurs frequently, especially if the examination is performed at 11 weeks. In such cases, when a delayed ossification is an isolated feature, it is recommended to wait and undergo a check-up examination after one week time. Usually, the calcification of the nasal bones improves and we can calm you and ourselves. However, if the ossification is still delayed, and the risk of genetic syndromes is increased, it is recommended to undergo a conclusive examination, i.e. chorionic villus sampling or amniocentesis.

In the first trimester we do not measure the length of the nasal bone, we evaluate the fetus for the presence or absence of the nasal bone and assess the calcification of one of the two nasal bones.

In our records, a delayed ossification of the nasal bones in the group of healthy fetuses we have observed so far in 2.6% of cases, in the group of the Down syndrome in 40.5%, in the group of the Edwards’ syndrome in 36.4%, in the group of the Patau syndrome in 50%, and in the group of the Turner’s syndrome in 44.4%.

A weak ossification of the nasal bones in the second trimester between 15 and 22 weeks is also considered an indication to perform amniocentesis. The difference in the assessment of the ossification in the second trimester consists in the measurement of the length of the bones (a correct value is 2.5mm) and the assessment of symmetry of both of them.

ad. 12. What does tricuspid regurgitation (=insufficiency=TR) mean?

Tricuspid insufficiency is a functional abnormality. This defect allows the blood to flow backwards, from the right ventricle to right atrium through the atrioventricular valve, also called the tricuspid valve. It may be due to an anatomical anomaly, although it is most often a symptom of an overload of the right ventricle. An isolated tricuspid insufficiency of a minor degree is a variation of the norm, which disappears after some time. It often occurs after and during an increased activity of a fetus. According to our records, it appears even in 6.4% of healthy fetuses examined in the first trimester, however, when it comes to the genetic syndromes, it occurs in 42.9% of fetuses with the Down syndrome, in 63.6% with the Edwards syndrome and in 50% with the Patau syndrome, usually in combination with other characteristics. A substantial tricuspid insufficiency might increase the risk of genetic syndromes. Therefore, only an experienced sonologist, holding a certificate in detecting tricuspid insufficiency (the list of examiners can be found on the FMF website) is able to decide whether the insufficiency might be identified as a genetic marker because a lot of insufficiencies are trivial and should not be included into the patient’s risk. It is worth to analyze all ultrasound and biochemical parameters. It allows to optimize the further course of pregnancy and select only those patients, who need to undergo a more detailed examination, i.e. chorionic villus sampling or amniocentesis. If a specialist does not diagnose additional, suspicious symptoms, such as an increased speed of the flow through a pulmonary artery or an increased NT, a patient might stop worrying.An isolated insufficiency disappears in almost 100% of cases and it is not observed in the second trimester. We tell our patients that “the baby grew out of the tricuspid insufficiency”. It is worth to verify the flow through a pulmonary artery and the ductus arteriosus to make sure there are no characteristics of a right ventricular overloading.

Negative “a wave” in the spectral waveform of the flow through ductus venosus (a tiny vessel in a fetal liver accelerating blood flow in the direction of the heart) is an extremely rare ultrasonographic finding. In our records, it occurs in 1.1% of healthy fetuses. In fetuses with genetic syndromes it occurs much more frequently, usually in combination with other genetic markers: in cases of the Down syndrome the negative a wave occurs in 33.3%; of the Edwards syndrome in 54.5%, of the Patau syndrome in 50%, of the Turner syndrome in 22%, basing on our own records.

The problem with examinations in the first trimester is a lot of over-diagnosis. Ductus venosus is a tiny vessel and a fetus is often very active in the first trimester. It is the reason for an increased frequency of an abnormal spectral waveform of the flow through ductus venosus if examined by a less experienced specialist. The assessment and the consultation is even more complicated in case of a fetus with a functional or even an anatomical absence of ductus venosus, frequently observed in children with the genetic risk.

At our centre, if we diagnose a negative “a wave” in ductus venosus together with an increased genetic risk, we recommend a conclusive examination. If the negative a wave does not influence the risk, we recommend an examination of an early fetal anatomy with the assessment of genetic risk and the fetal heart already at 16 weeks of pregnancy.

ad. 14. Choroid plexus cysts. What does it mean?

Cysts are a kind of widening of choroid plexus. Choroid plexus cysts are not a brain defect on their own, and as an isolated characteristic, are a part of the physiology of fetal development. For this reason, they do not require a second opinion and they disappear usually around 26 weeks of pregnancy.

If a sonologist diagnoses choroid plexus cysts, he is obliged to perform a more detailed assessment. It is essential to verify whether there is spasticity of hands (hard-clenched hands during the whole examination), umbilical cord cyst, umbilical hernia and heart defects. Coexisting with these symptoms might indicate a genetic syndrome (e.g. trisomy 18) and it requires performing additional tests.

ad. 15. What is hyperechogenic intracardiac focus in a fetal heart?

Echogenic intracardiac focus (also called hyperechogenic or a bright “spot”) is a rather common ultrasound image occurring in ab. 3% of healthy fetuses. It is not a heart defect or a calcification. This image comes from reflection of ultrasounds from a rough surface of chordae tendineae (structures joining valve of the heart with its muscles) and with certain positions of the apparatus transducer it may produce an impression of a small bright nodule. It is a variation of the norm and does not require highly specialized consultations or monitoring.

ad. 16. Single umbilical artery – what is it?

Single umbilical artery is an issue occurring when one of the two arteries running deoxygenated blood from a fetal body to a placenta had not developed or gradually disappeared. Then, one of the arteries expands compensating the absence of the other. If such an image appears in an ultrasound examination without combination with any other anomaly it is a variation of the norm occurring in ab. 1% of healthy fetuses.

At that time, it is recommended to exclude defects of the urinary system, of the fetal heart, and the presence of hard-clenched hands or umbilical hernia, which might indicate genetic syndromes.

ad. 17. What is understood by the “risk” of the Down syndrome?

Every woman has her own initial (basic) risk of having a child with the Down syndrome. It increases along with her age. In the 1970s it has been assumed that the age of 35 is a critical age, and it implies a high risk of genetic disorders and constitutes an indication for diagnostic prenatal examinations. Now we know, that basing only on the age of a mother we are able to detect maximum of 30% of babies with the Down syndrome. Why is that? A group of pregnant women at the age of 35 and above comprises just 20% of all the pregnant women. The rest of 80% are younger women who will give birth to 70% of babies with this disorder. Therefore, it has been accepted that screening tests have to include all pregnant women, and the age of a mother shall be one of the factors influencing the final risk of genetic disorders.

Screening tests may be performed on the basis of an ultrasound examination (a measurement of nuchal translucency, among others), a biochemical examination from a blood sample of a pregnant woman (levels of two hormones in blood serum: free subunit β-HCG and PAPP-A) or combine both into a so-called Combined Screening Test based on the age of a pregnant woman, a value of nuchal translucency and values of hormones in a woman’s blood sample. It is best when the examination covers all sorts of ultrasonographic parameters (the ossification of the nose, the function of a tricuspid valve, the flow in a ductus venosus, and possible identified defects). Such a test is characterized by the highest effectiveness in the first trimester. In a report from the test, under the calculation of the risk, in a small print there is a list of all the parameters taken into consideration during calculations. The result of the combined test is a numerical value (fraction) with a comment, qualifying the patient to a group of a low or an increased risk. Patients who find themselves in the group of an increased risk will be proposed a prenatal examination which excludes chromosomal aberrations with 100% certainty.

Let us analyze two example results of screening tests towards the Down syndrome:

1/3,547 – this value tells us that 1 in 3,547 women at the same age, with an identical obstetric history, the same ultrasound image and similar biochemical parameters may give birth to a baby with a disorder. It is a very good result meaning that the probability of having a genetically healthy child is very high;

1/24 – this value tells us that 1 in 24 women at the same age, with identical obstetric history, the same ultrasound image and similar biochemical parameters may give birth to a baby with a disorder. It is not similar to diagnosis, it only indicates that a screening test was not sufficient and there is a need for a prenatal examination, which is e.g. chorionic villus sampling or amniocentesis.

ad. 18. How to prepare for an ultrasound scan?

An ultrasound scan does not require any preparation in general. In case of an scan during pregnancy we advise to empty the bladder before entering the consulting room. On the day of an examination, it is important to avoid using any crèmes or dermatological specimens on the skin of the abdomen as they may reduce penetration of the ultrasound beam. Women with excessive hairiness on the surface of the skin of an abdomen are politely asked to remove hair, which reflects ultrasound beams and limits the view, which, in turn, decreases the effectiveness of the examination.

Transvaginal ultrasound scan requires emptying the bladder. In cases of young girls and women who have not had sexual intercourse yet we perform a transabdominal examination, and therefore, it is important to fill the bladder well before the examination (e.g. 1l of mineral water 30 minutes before the examination).

ad. 19. A double, triple, quadruple test – what it is, is it necessary and how to interpret results?

The first examinations towards the Down syndrome were based on marking an AFP hormone in a serum. If the result was lower than expected, it was treated as suspicious. A weak sensitivity of these markers caused adding another parameter called β-HCG. That is how a double test came into existence (in Polish literature commonly mistaken with the Combined Screening Test in which PAPP-A + fβ-HCG are assessed), which, nevertheless, did not increase the sensitivity in a significant way. Next, the assessment of the estriol value was added, and the examination was called the triple test.

The triple test measures serum levels of above-mentioned AFP, estriol, and b-hCG and is best performed between 16 and 18 weeks of gestation. After obtaining quantity values, the values in respect of a population (MoM) are calculated in a lab and on their basis the risk of the Down syndrome and the defects of so-called neural tube is determined. The result is treated as suspicious in terms of the Down syndrome when the values of AFP and/or estriol are below 0.7 MoM, and the value of β-HCG is above 2 MoM. In some laboratories yet another parameter is added – dimeric inhibin A (suspicious if the value exceeds 2 MoM), then the test is called a QUAD screen test.

Despite combining several parameters the sensitivity of a triple test is still weak. The triple test is less effective in comparison to a screening test in the first trimester of pregnancy even if it is based only on the measurement of nuchal translucency and the age of a pregnant woman. It gradually becomes the history of diagnostics. The triple test has a substantially weaker sensitivity than a combined test (age + NT + PAPP-A + fβ-HCG). It is also less sensitive than a second trimester “genetic” sonogram.

In some centres in the world a so-called Integrated Test is carried out, which consists in calculating the risk of the Down syndrome on the basis of the age, nuchal translucency, PAPP-A from the first trimester and β-HCG, AFP and estriol from the second trimester. A patient receives the final result not until the second trimester, unless the parameters of the first trimester are extremely alarming. This delay of the result from an integrated test made the combined test to be the international standard of examination towards the Down syndrome.

ad. 20. What do specialists understand by the word “marker”?

Marker is a structural defect, image or sonographig measurement associated with a fetus with a genetic disorder. Defects are called major markers. Examples are umbilical hernia or abnormal fingers positioning of both hands in the Edwards’ syndrome, i.e. trisomy 18. Images and measurements are called soft markers. They occur more frequently in babies with genetic disorders, however, they may appear in rare cases of healthy fetuses. An example of this can be a sandal gap deformity (which is an increase in the interspace between the great toe of the foot from the rest of the toes), a shorter thigh bone (which is typical for the Down syndrome) or an increased nuchal fold thickness (characteristic of the Down syndrome but also of other disorders). An isolated occurrence of soft markers is observed quite often and is not an indication for an invasive test. Coexistence of several such markers is alarming and requires considering genetic tests.

ad. 21. Monochorionic diamniotic twin pregnancy. Should the ultrasound examination be performed more frequently?

If a monochorionic diamniotic (with two babies’ “homes”) twin or multiple pregnancy (with one placenta) is confirmed, it is essential to undergo a more frequent ultrasound examination! Between 16 and 24 weeks, every two weeks, it is necessary to assess the volume of the amniotic fluid of both fetuses, in order to exclude complications connected with this type of twin pregnancy (twin-to-twin transfusion syndrome – TTTS, occurring in ab. 5-10% of cases). It is very important to diagnose an abnormality possibly quickly so there is sufficient time to employ an appropriate procedure.

Often (in ab. 30% of monochorionic diamniotic pregnancies) in the third trimester of pregnancy selective intrauterine growth restriction of one of the twins is observed. A regular monitoring of fetuses is necessary in such a case.

ad. 22. Does it change anything if I undergo amniocentesis or chorionic villus sampling?

During discussions with our patients who have indications for chorionic villus sampling or amniocentesis very often they ask the question: “What does it change if I receive a result of a karyotype?” Frequently, it is a repercussion of an opinion of another person, family or a physician. Here are some arguments, depending on a situation:

a reliable karyotype result changes a lot! It might give the greatest peace of mind. Naturally, insecurities, especially regarding the risk of genetic disorders, tend to return causing major uncertainty during following examinations. It should be clearly stated that most of conclusive examinations are correct and each patient has a great chance of receiving an information that their baby is genetically healthy.

in case of congenital defects, e.g. heart defects, it is very important for further prognosis to exclude a genetic background of this anomaly.

amniocentesis/chorionic villus sampling should not depend on the possible decisions about the further course of the pregnancy. We are against looking ahead to the future. We consider it a great mistake when talking to and consulting our patients. In a lot of cases the karyotype result cannot be predicted and only after receiving it a proper discussion might take place.

And what about the risk of complications and even a miscarriage after the examination? The method of sampling for amniocentesis or chorionic villus sampling employed at our centre is very safe. Therefore, patients should pay more attention to the benefits coming from a procedure in the form of an assessment of the baby’s chromosomes than to the anxiety caused by the procedure itself.

ad. 23. What is the advantage of chorionic villus sampling over amniocentesis?

The main advantages of this examination are time and safety! Chorionic villus sampling can be performed a lot earlier, thus gaining several precious weeks (on average, the result is ready a month before the result from amniocentesis). The optimal time to undergo the examination is completed 11 weeks (11+0) which overlaps with a screening test of the first trimester (nuchal translucency + biochemical exam).

In respect of the fact that an inserted needle does not enter an amniotic cavity, i.e. the baby’s “home”, the examination is seen as safe all over the world. The latest research indicates a high safety of chorionic villus sampling. The study was based on the population of about 10,000 women. It was observed that among patients who underwent chorionic villus sampling there were less cases of miscarriage (excluding termination of pregnancy for medical reasons)!

Nowadays, the assessment of an AFP level in the amniotic fluid, which is carried out during the amniocentesis does not contribute anything to the result. At present, defects such as split spine or gastroschisis can be detected during an ultrasound scan even in 100% of cases.

Patients who decide to undergo a conclusive examination at our centre receive full guarantee that the sample collection will be performed by specialists experienced in this field: dr. Wiecheć and/or dr. Nocuń. We do sampling regularly, at least once a week. We hold the highest efficiency in chorion culture in Poland, which proves not only laboratory experience but also optimal collection of material for a test (we had only 2 failures in chorion culture). We maintain extremely low percentage of pregnancy losses (in the last 5 years: 0 losses after amniocentesis; 0 losses after NT of less than 6mm; 4 losses after chorionic villus sampling – including 2 cases of the Edwards’ syndrome with a vast edema with NT of 6mm; 1 case of the Turner syndrome with a hydrops fetalis and NT=8.1mm; 1 case of extensive umbilical hernia containing a liver, without chromosomal aberrations). All of these losses could have been caused by serious congenital defects. Safety and efficiency of sampling is certified at our centre by the most difficult to obtain certificate of competence in invasive procedures awarded by the Fetal Medicine Foundation (requires a documentation of the number of performed procedures, as well as taking theoretical and practical exam at one of the leading European clinics). For procedures, we employ highest quality needles with tips reflecting ultrasounds, i.e. an echo tip, in order to maintain the same standards of material collection as in the top American clinics.

The laboratory section is covered by a team of cytogeneticists KARIOGEN with over 20 years of experience in growing cells, teaching other specialists in this field for years. The factors of time and comfort are important as well. We are able to collect a sample on the same day, not wasting time for referrals and additional examinations (apart from the blood type), or obstetric and genetic consultation as in a state hospital, where the procedure is usually connected with a long waiting time and a journey. All our samples end up in the lab within an hour using our own transport. The prices of examinations are adjusted to minimize the cost for our patients.

Patients with Rh-Negative blood type are provided with anti-D immunoglobulin.

We are responsible for our actions, therefore, our patients are always presented with an option, which is, in our opinion, the safest and the quickest. It is impossible for us to be responsible for examinations performed at other centres, whether state or private, and for that reason, we do not raise the issue of “other options” during consultations.

In regard to the question: “Is contamination of a chorionic villus sampling sample by mother’s cells possible?” and to widely spread, not scientifically proven opinions of people (including physicians) concerning this issue, we will try to explain it as exhaustively as possible.

In cells culture only slight contaminations from mother’s cells may appear. According to research, it is about 1.8% – 4% of sample’s volume. Mother’s cells look different under an inverted microscope, and therefore, in an experienced laboratory they are easily detected and separated. Thus, in chorion cells growth only fetal chorionic villus samples are used. Contamination of the sample with a patient’s blood has no influence on the culture of chorion cells.

Irrespective of the culture, we always try to compare the genetic result from the chorionic villus sampling with an ultrasound scan. We encourage all patients, who underwent a diagnostic test at our centre, to have a detailed ultrasound examination in the second trimester as well. In case of any doubts concerning the health of a fetus with a normal genetic test result, we will consider collecting another sample. If a patient underwent chorionic villus sampling, this time we would suggest amniocentesis, and if a patient underwent amniocentesis, we would suggest fetal blood sampling. The situation described above hardly ever takes place and it aims to reassure our patients about the reliability of the results.

ad. 26. Is initial karyotyping with cells from a chorionic villus sampling possible in one day?

For a quick assessment targeting techniques, aimed at chromosomes 21, 18, and sex chromosomes, can be used. Most widely used are FISH and QF-PCR. Much more precise and a faster method is the direct overnight karyotyping technique, which allows for initial assessment of all chromosomes with the use of the material from a chorion.

A sample from chorionic villus sampling or amniocentesis might also be sent to assessment with the use of the comparative genomic hybridization (CGH) by a geneticist cooperating with our centre. The CGH results are available within a week.

At our centre, we offer a wide range of examinations and methods, their choice depends on the patient’s will, geneticist’s suggestion and a technical possibility to collect a sample.

ad. 27. When to undergo chorionic villus sampling?

Chorionic villus sampling (CVS) can be performed safely after completed 11 weeks of pregnancy (11+0) until delivery. There is no upper limit of gestational age restraining the possibility to carry out the sampling, though the tendency is to perform this examination up to 14 weeks. However, there are situations after 14 weeks, in which chorionic villus sampling is an optimal solution. The oligohydramnios or anhydramnios are good examples. In the following cases, there is no possibility for collecting amniotic fluid or it might be unsafe. In such cases, after 19 weeks umbilical cord blood might be extracted through cordocentesis.

ad. 28. Can chorionic villus sampling cause defects in the development of fetal limbs?

Chorionic villus sampling carried out after 11 weeks, does not influence the development of limbs and does not cause any defects. In very old reports concerning chorionic villus sampling, when it was performed very early, i.e. at 8 or 9 weeks, defects in limbs development in some individual cases were detected. Therefore, nowadays, early chorionic villus sampling is not performed.

The method of collecting samples ensures that the amniotic sac is protected and thus it means no defects in limbs, which are fully developed after 11 weeks of gestation.

ad. 29. When to undergo amniocentesis?

This examination is performed after 15 weeks of pregnancy (15+0). It is worth to mention that there is a possibility to perform cordocentesis after 30 weeks. Such an examination is offered to patients who did not decide on amniocentesis between 15 and 16 weeks of pregnancy in fear of miscarriage. After 30 weeks there is only a slight risk of an early birth with nearly 100% of survival.

ad. 30. What are the recommendations for before and after the amniocentesis/chorionic villus sampling?

Apart from a positive attitude, there are no recommendations for patients before the amniocentesis or chorionic villus sampling. These examinations should be treated in the same manner as other extractions such as puncture of an elbow pit for acquiring a blood sample from a mother.

Please be sure to provide us with an original patient’s blood group certificate. Before the examination we recommend a genetic consultation, which in a lot of cases might help to optimize the method of a sample collection.

In recent years the technique of material sampling has changed. It is much safer, and the needles used are significantly thinner. Therefore, let us emphasize that complications after diagnostic tests are extremely rare, thus after this kind of procedures no specific recommendations are given.

The risk of complications is the highest during first two days after the procedure. Patients should avoid physical strain at the time. If there are no major issues during this time, the risk of pregnancy loss drops nearly to zero. OTC medications allowed in case of a discomfort after the procedure are “Paracetamol”, “Buscopan”, “No-Spa”. The risk disappears completely after about two weeks.

In case of any distressing symptoms such as: frequent regular abdomen pain, spotting, bleeding, amniotic fluid leak or increased temperature, a contact with the specialist in charge, our centre or the nearest obstetric centre is recommended. Please remember that some spotting might occur during pregnancy, which is not related to the performed procedure. A consultation with a gynecologist will help to soothe nerves.

The risk of pregnancy loss is always higher in case of fetal edema or complex congenital defects.

Culture in case of chorionic villus sampling or amniocentesis takes about 2 – 3 weeks and from umbilical cord blood ab. 4 days. After receiving the result from a laboratory, a direct contact with the patient is made to arrange a meeting to deliver the results.

ad. 32. What is the Down Syndrome?

It is an incurable genetic disorder conditioned by the presence of additional, third chromosome 21, thus called trisomy 21. The frequency of appearance in a population is ab. 1 in 1,000 live births. The Down syndrome is connected with different levels of mental impairment, more frequent congenital defects, most commonly atrioventricular septal defect, alimentary canal defects such as duodenal atresia and the Hirschsprung’s disease, leukemia, hydrocephalus, microcephaly, dismorphic face, urinary tract defects and a number of typical appearance characteristics. The only method of verifying the Down syndrome is the chromosome assessment, which in a fetal life is carried out with the use of amniocentesis, chorionic villus sampling or fetal blood sampling; and after birth on the basis of a baby’s blood test.

ad. 33. What is more important: the specialist or the ultrasound scanner?

We would like to very specifically and comprehensively answer this question. We agree with the opinion that either a specialist without the medical equipment, or the scanner without the specialist cannot perform an examination. We confirm that the quality of the equipment is of a great importance, thus we operate on the most advanced ultrasound scanners. However, we would like you to be aware that many factors influence a proper ultrasound examination, depending on the experience and professionalism of a specialist and not on the equipment:

clarity of obtained images, i.e. the technique of the equipment adjustment. All the ultrasound scanners are preset for a typical patient, although, as we well know, patients are very different, the amount of amniotic fluid is different (acoustic window), also the positioning of a baby and placenta can vary. Adjusting the equipment to the conditions of an examination is the role of a specialist and the knowledge to acquire in this field is very extensive;

the knowledge in the area of the correct anatomy and its anomalies in imaging is acquired during a diagnostic training of a given specialist. The apparatus cannot differentiate a healthy heart from the one with a defect, however a good specialist can.

A lot of patients ask us if we learned ultrasonography at a university. This competence is not a part of a college curriculum and is treated as an individual qualification of a physician.

ad. 34. How to plan ultrasound examination in the second trimester if I am a high BMI woman?

Among people with extensive amount of subcutaneous tissue, ultrasound penetration is weakened, and a fetus is located in a greater distance from the abdominal surface and the transducer. In such cases, a sonologist assesses fetal structures distantly, like through a fog, which is a great impediment. Most patients, and even a number of physicians in charge do not realize the problem.

A scan of each patient should be performed with the same precision. Therefore, it is good to prepare a scan of a high BMI patient well. We propose to carry out the examination of the second trimester in two stages: the first stage at around 16 – 17 weeks, when a vaginal access is still possible and the second stage at around 20 weeks. When it comes to costs, we treat this kind of situation as one examination. That kind of approach simplifies the matter and gives the patient a guarantee that a baby was examined accurately. In case of any doubts it is worth asking the sonologist during assessment in the first trimester if a transabdominal ultrasound scan will not be hindered in the second trimester.

ad. 35. 3D ultrasound: is it just a trend or something more?

A commonly known use of a 3D in ultrasound is a so-called baby face, i.e. a type of imaging of a surface which allows for a preview of a baby’s face, mouth movement, limbs or sexual organs. It has nothing in common with the real concept and purpose of a 3D ultrasonography, but is often only a neat addition to an examination. Medical, 3D ultrasound scan consists in storing a baby’s body or woman’s reproductive organ in a form of volume blocks and analyzing downloaded data off-line, without participation of a patient, using expert computer software. In the world, 3D techniques found their application in specifying a diagnosis in case of detected defects of a fetus and in gynecological examinations. In Poland, only few centres employ them in full scope. At our centre, 3D ultrasound is an essential element of a scan, mainly in cases of complex fetal defects, congenital defects and reproductive organ pathologies. In extremely rare cases, an analysis of stored data takes place without a patient. Then, we compare images on the basis of our own record and volumes concerning complex anomalies. This allows to fully minimize a patient’s discomfort connected with an examination concerning an assessment of anomalies.

ad. 36. What is so special about our scanning technique?

We cooperate with engineers and specialists in ultrasonographic software for leading manufacturers of ultrasound equipment in order to fully use ultrasonographic equipment for purposes of our own and our patients. Thanks to their knowledge and our experience our images are clean and clear. We guarantee that every patient can tell the difference in the quality of our images, which does not come from using a special ultrasound scanner. We are skilled in using the whole range of corrective filters in order to adjust the image individually to every patient. On only currently applied settings, we have been working for the last 3 years, comparing examination conditions for different patients. We apply the experience in modern imaging techniques onto the manner of moving over a scanner transducer, which causes our examinations to be very efficient in a relatively short time. We are up to date with new ultrasound software of different manufacturers introduced each year. Several times a year we compare the potential of different ultrasound scanners and different transducers. On that basis, a lot of specialists in Poland and abroad take our opinions into consideration before ordering new ultrasound equipment.

The technique of examination, which we employ, is not insignificant. Specialists, lecturers, and instructors who teach medical staff in Poland and abroad work at our centre. Our centre equals practice created by ultrasound teachers. It distinguishes us from other centers.

ad. 37. My baby has suspected anomaly. What does it mean?

If during an ultrasound scan a specialist suspects an anomaly, it is crucial to perform a specialist ultrasound scan. Its aim is to exclude or confirm the existence of a defect and precisely determine its kind, level and possible coexistence of other anomalies. At our centre, in case of defects confirmed by us, we propose genetic assessment, and in some cases, consultations with pediatricians to plan a further course and a treatment of a newborn baby.

ad. 38. What does it mean to review the images without the presence of a patient?

Volumetric techniques such as 3D, 4D and STIC allow to review stored volume blocks both on an ultrasound scanner and on a computer with a help of a designated software. It is possible without the presence of a patient and gives an opportunity for consultations and joint consultations also through the Internet. For a few years, we have been using a licensed software. In case of every patient who has a rare fetal defect, a reproductive organ defect or a suspected anomaly, we capture a number of images which are later reviewed without a patient. Such a model of an examination significantly reduces the time of a consultation and a patient’s discomfort, allowing us to fully concentrate on an accurate diagnosis.

ad. 39. What is 2D, 3D, 4D and STIC?

2D examination consists in imaging using ultrasound, which are safe for a fetus. An obtained image is flat, being a cross-section of an analyzed body part of a patient in a plane seen by a transducer. 3D is a three-dimensional image, partly reconstructed and acquired from an image of a part of a patient’s body in a form of a block of data containing many 2D cross-sections in three perpendicular planes. Such blocks can be analyzed additionally in a form of a three-dimensional reconstruction set on external, skeletal or vascular structures. 4D are the 3D images updated in time. This allows to visualize fetal movements. STIC is a kind of a 4D imaging intended for a heart. It consists in recording the whole heart in a form of a block of data during about 20 cardiac cycles. This technique is irreplaceable in case of suspected congenital heart defects. STIC is an echocardiography of the future, requiring from a specialist not only medical knowledge but also an acquaintance with modern ultrasonographic techniques.

ad. 40. What is 2D imaging in a B mode?

It is a typical, commonly used 2D imaging. It allows for an assessment of planes marked by a transducer, so-called ultrasound cross-sections. Moving a transducer over creates new planes. We scan a given structure a cross-section after a cross-section, which allows us to assess it very accurately.

ad. 41. What is a color Doppler?

It is imaging, which with a help of color tones (e.g. red and blue) allows to assess a direction and, indirectly, speed of a blood flow in vessels and heart cavities. It is an essential technique during a fetal heart examination. It allows to visualize filling of ventricles and the activity of the heart valves. Thanks to its sensitivity, the color Doppler gives an opportunity to diagnose small defects in e.g. a ventricular septum, non-typical tubular connections or precisely expose small vessels difficult to localize through 2D imaging in a B mode.

ad. 42. What is a spectral Doppler?

The spectral Doppler is designed to assess the nature and speed of a blood flow in vessels or heart valves. On the screen, it is presented as regular waves of the frequency of a fetus’s heart or a heart of a mother if her vessels are examined. In everyday practice, in the third trimester of pregnancy, we use it in assessment of a flow in an artery of a fetal brain, in an umbilical artery in an umbilical cord, in a vessel in a liver and for the assessment of a baby’s circulatory system, i.e. an assessment of a baby’s well-being. Depending on the oxygen conditions and the level of carbon dioxide in fetal blood, the shape and the nature of the wave change. An ability to interpret the wave properly is extremely important and requires a great experience from an examining specialist. What is more, the spectral Doppler is applicable in an examination of a fetal heart, it allows for an early suspicion of a slight vessel stenosis, assessing the rhythm and the activity of atria, ventricles and valves in a heart. In an examination of a mother’s uterus artery, it allows for an early detection and placing women in the risk group of pregnancy induced hypertension.

ad. 43. What is tomographic imaging?

It is a mode allowing to review stored 3D images in a form of parallel cross-sections (three, five, eight or more) of an examined part of a body, e.g. fetal chest. The term “tomographic ultrasound imaging” or “multi-slice view” fully expresses the concept of the method, very similar to classic computed tomography used in radiology.

ad. 44. What does a tissue Doppler mean?

It is a function of a Doppler used increasingly more often in echocardiographic scans among adults for an assessment of a heart contractility which can be impaired after, e.g. a heart attack. It is applied in obstetrics in a similar way. Congenital defects belong to the most common causes of a heart contractility impairment in a fetal life. The tissue Doppler, with the help of color, shows a contracting heart with a high sensitivity, allowing for a better detection of possible anomalies.

ad. 45. What is imaging in an M mode?

It is one of the oldest modes in ultrasonographic imaging employed in echocardiographic scans of children and adults for assessment of contractility, the width of cavities, walls thickness and the rhythm of a heart. The M-mode consists in obtaining a dynamic cross-section of the heart cavities, which then is analyzed over the time. An M presentation is used in obstetric examinations for assessment of the rhythm and contractility of a fetal heart.